title: Effects of simvastatin on cytokines secretion from mononuclear cells from critically ill patients with acute kidney injury.
abstract: OBJECTIVE
  To assess the in vitro effects of simvastatin on IL-10 and TNF-α secretion from peripheral blood mononuclear cells (PBMC) of critically ill patients with and without acute kidney injury (AKI).
  
  
  METHODS
  PBMC were collected from 63 patients admitted to the intensive care unit (ICU) and from 20 healthy controls. Patients were divided in 3 subgroups: with AKI, with sepsis and without AKI and with AKI and sepsis. After isolation by ficoll-gradient centrifugation cells were incubated in vitro with LPS 1 ng/mL, simvastatin (10(-8)M) and with LPS plus simvastatin for 24h. TNF-α and IL-10 concentrations on cells surnatant were determined by ELISA.
  
  
  RESULTS
  Cells isolated from critically ill patients showed a decreased spontaneous production of TNF-α and IL-10 compared to healthy controls (6.7 (0.2-12) vs 103 (64-257) pg/mL and (20 (13-58) vs 315 (105-510) pg/mL, respectively, p<0.05). Under LPS-stimulus, IL-10 production remains lower in patients compared to healthy control (451 (176-850) vs 1150 (874-1521) pg/mL, p<0.05) but TNF-α production was higher (641 (609-841) vs 406 (201-841) pg/mL, p<0.05). The simultaneous incubation with LPS and simvastatin caused decreased IL-10 production in cells from patients compared to control (337 (135-626) vs 540 (345-871) pg/mL, p<0.05) and increased TNF-α release (711 (619-832) vs 324 (155-355) pg/mL, p<0.05). Comparison between subgroups showed that the results observed in TNF-α and IL-10 production by PBMC from critically ill patients was independent of AKI occurrence.
  
  
  CONCLUSIONS
  The PBMC treatment with simvastatin resulted in attenuation on pro-inflammatory cytokine spontaneous production that was no longer observed when these cells were submitted to a second inflammatory stimulus. Our study shows an imbalance between pro and anti-inflammatory cytokine production in PBMC from critically ill patients regardless the presence of AKI.
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Gabriela Laender
authors.initials: GL
authors.lastname: Ferrari
authors.forename: Beata Marie Redublo
authors.initials: BM
authors.lastname: Quinto
authors.forename: Kelly Cristina Batista de Souto
authors.initials: KC
authors.lastname: Queiroz
authors.forename: Ilson Jorge
authors.initials: IJ
authors.lastname: Iizuka
authors.forename: Julio Cesar Martins
authors.initials: JC
authors.lastname: Monte
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Dalboni
authors.forename: Marcelino Souza
authors.initials: MS
authors.lastname: Durão
authors.forename: Miguel
authors.initials: M
authors.lastname: Cendoroglo Neto
authors.forename: Oscar Fernando Pavão
authors.initials: OF
authors.lastname: dos Santos
authors.forename: Marcelo Costa
authors.initials: MC
authors.lastname: Batista
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D016022:Case-Control Studies; D016638:Critical Illness; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019821:Simvastatin